Synergistic combination of a halogenated bisphenol and a polyhalo-salicylanilide



United States Patent Oce 3,445,397 Patented May 20, 1969 U.S. Cl. 252106 10 Claims This invention relates to antiseptic compositions having synergic effect. In one of its aspects, this invention relates to improved germicidal cleansing compositions containing as their essential active germicidal ingredients a synergistic combination of a halogenated bisphenol and a polyhalo-salicylanilide.

This application is a continuation-in-part of our copending application Ser. No. 739,477, filed June 3, 1958, now abandoned.

The popularity of germicidal cleansing compositions for laundry and toilet use has increased tremendously over the past few years. In fact, it has been estimated that 20 percent of the bar soap sales now are of products containing a germicidal agent, and this percentage is steadily increasing. There are a number of germicidal agents currently in use but the halogenataed bisphenols appear to be the most widely accepted because of their activity, compatibility, and commercial availability. One of the desirable compounds of this class is 2,2-dihydroXy-3,5,6,3,5', 6'-hexachlorodiphenyl methane, commonly known as hexachlorophene, which is now in widespread commercial use. Another example is 2,2'-dihydroxy-3,5,3',5-tetrachlorodiphenyl sulfide, commonly known as bithionol. The action of halogenated bisphenols such as hexachlorophene when incorporated in soap, the proportions required, and other pertinent information, is set out more fully in US. Patent No. 2,535,077 to Kunz et 211.

There are certain inherent disadvantages to the use of halogenated bisphenols. For example, they are photosensitive and tend to cause discoloration in the finished product upon exposure to light. They are somewhat toxic and present a potential hazard to domestic animals which are prone to eat things, even soap, Therefore, it would be desirable to diminish these disadvantages without adversely affecting the germicidal activity of the halogenated bisphenol. Viewed in a different light, it would also be worth while if these disadvantages could be maintained at their present level and the germicidal activity of the halogenated bisphenol increased. We have discovered that these objects can be accomplished through the production of a synergic effect.

In accordance with the present invention, the germicidal effects of antiseptic compositions containing halogenated bisphenols are enhanced, synergized, or potentiated by incorporation therewith a polyhalo-salicylanilide. The products of the invention, therefore, are antiseptic compositions containing as their essential active ingredients a synergistic combination of a halogenated bisphenol and a polyhalo-salicylanilide. The halogenated bisphenols used in accordance with the present invention can be represented according to their chemical structure as follows:

HO OH E Xn Xn wherein X represents a halogen such as chlorine or bromine, n is an integer of from 1 to 3, and R represents a divalent radical including alkylene radicals having 1 to 4 carbon atoms such as -CH CH CH CH CH CH etc., and S. The preferred compounds are symmetrical in structural configuration. Specific examples of the halogenated bisphenols include compounds such as 2,2-dihydroxy-3,5,6,3',S,6'- hexachlorodiphenyl methane, 2,2-dihydroxy-3,5,3',5'- tetrachlorodiphenyl methane, 2,2-dihydroXy-4,5,4',5'- tetrachlorodiphenyl methane, 2,2-dihydroxy-3,4,3',4'- tetrachlorodiphenyl methane, 2,2'-dihydroxy-5,5'-dibromodiphenyl methane, 2,2'-dihydroxy-3,5,3',5-tetrachlorodiphenyl sulfide and 2,2'-dihydroxy-5,5-dichlorodiphenyl sulfide.

The polyhalo-salicylanilides used in conjunction with the halogenated bisphenols in the present invention can be any suitable salicylanilide composition characterized by the presence of halogen atoms in both of the aromatic rings. These compounds can be represented according to their chemical structure as follows:

Q OH Y I I I wherein Q represents a member selected from the group consisting of hydrogen, chlorine, bromine, and iodine, X and X each represent a member selected from the group consisting of hydrogen, chlorine, bromine, iodine and CH X represents a member selected from the group consisting of hydrogen, chlorine, bromine and CH and X and Y each represent a member selected from the group consisting of hydrogen, chlorine and bromine, there being at least two halogen substituents in the X positions. Specific examples of compounds coming within the afore mentioned general formula include S-chlorosalicylic acid- 3',4'-dichloroanilide, 5-chlorosalicylic acid-4-chloroanilide, 4,5'-dichlorosalicyclic acid-3',4-dichloroanilide, 4,5- dichlorosalicylic acid-2',3',4'-trichloroanilide, and 3,5-dichlorosalicylic acid-2',3',4'-trichloroanilide. These compositions are produced, generally, by the reaction between a halogenated salicylic acid and a halo-substituted aniline.

It has been found that when the halogenated bisphenols and the polyhalo-salicylanilides, as illustrated above, are used together in an antiseptic composition, a germicidal effect is achieved which is greater than the mere total of the individual effects of the individual ingredients. This has importance in cases where the activity of the halo genated bisphenhol is desired to be increased without employing higher concentrations, and in other cases it assumes an even greater importance from an economic standpoint, since the presence of the polyhalo-salicylanilides enables a substantial reduction in the concentration of the germicidal agent while at the same time retaining the desired level of germicidal effect,

What the actual mechanism of the potentiating or synergistic elfect might be, we are unable to explain. The invention relates to the synergistic cooperation of these two types of compounds when used in minor proportions in antiseptic compositions, especially antiseptic detergent compositions, and the discovery that this synergistic phenomenon occurs even at the high pH conditions existing in soap and detergent formulations provides one of the important phases of the present invention.

Relatively small amounts of the halogenated bisphenol and polyhalo-salicylanilides are sufficient for the increased germicidal etfect of the present invention. Satisfactory results are obtained in antiseptic detergent compositions when the combined weights of the two types of compounds are from 0.05 to 5.0 percent of the total weight of the soap or detergent. The objects of this invention may be achieved when the weight of the halogenated bisphenol is about 0.1% to 3% and the polyhalo-salicylanilide is about 3% to about 0.1% of the soap or detergent weight. The preferred range is a weight concentration of about 0.25% to 1.75% of the halogenated bisphenol and about 1.75% to about 0.25% of the polyhalo-salicylanilide compound, and an excellent product is one containing soap and about 0.5% each of the halogenated bisphenol and the polyhalo-salicylanilide. It will be understood that even concentrations below the ranges just set out will provide some degree of germicidal effect and that substantially higher concentrations than those referred to above will provide satisfactory results, although there are certain technical considerations, such as the cost of the germicides and a certain impairment in detergent properties, which limit the desirability of including greater amounts of the germicidal compositions in the soap.

The ratio of the preferred range of the halogenated bisphenols to the polyhalo-salicylanilide is about -90% by weight of the halogenated bisphonels to about 90-10% by weight of the polyhalo-salicylanilide. In other words, in a soap containing a germicidal concentration of hexachlorophene or bithionol, the anobial is preferably used in the proportion of 10-90% by weight to 90-10% by by weight of the hexachlorophene or bithionol.

The term soap refers to the water-soluble ammonium, metallic, or organic base salts of various fatty acids, which are chiefly lauric, oleic, stearic, and palmitic acids. As used in the specification and claims, the term is intended to cover all products in which soap is a major constituent, for example bar, flake, powdered, soft, and liquid soaps; shaving creams, tooth pastes, cleansing creams, etc.

The invention also contemplates the use of anionic and nonionic-type synthetic detergents in place of the soap. The anionic-type synthetics suitable for use in the invention can be described as those detergents having pronounced cleansing power and including in their molecular structure an alkyl radical containing from 6 to 18 carbon atoms and a sulfonic acid or sulfuric acid ester radical. Organic base, ammonium, sodium, or potassium salts of the anionic-type detergents can be used. The main types of detergents falling within this category are the alkyl aryl sulfonates, such as sodium or potassium dodecyl benzene sulfonate, sodium or potassium octadecyl benzene sulfonate, and sodium or potassium octyl naphthalene sulfonate; the alkyl sulfates, such as sodium or potassium salts of dodecyl, hexadecyl, and octadecyl sulfates; the sulfonated fatty acid amides, such as sodium or potassium salts of the oleic acid amide of methyl taurine; and the sulfonated monoglycerides, such as the monococonut oil fatty acid ester of 1,2-hydroxypropane- 3-sodium sulfonate.

The nonionic-type synthetic detergents suitable for use in the invention may be described as those detergents which do not ionize in solution but owe their watersolubility to unionized polar groups such as hydroxyl or ether linkages. The main types of detergents falling within this category are the polyoxyethylene ethers of the higher fatty alcohols and alkyl phenols; the polyethylene glycols of fatty acids; fatty alkylol amide condensation products; polymers of ethylene and propylene oxides; compounds formed by the addition of propylene oxide to ethylene diamine, followed by the addition of ethylene oxide; fatty acid ethylene oxide condensation products; condensation products of ethylene oxide and a fatty acid ester of a polyhpdric alcohol or sugar; and the detergents prepared by heating together a higher fatty acid with a dipared by heating together a higher fatty acid with a diethanolamine. Some examples if synthetic nonionics suitable for the purposes of this invention are ethylene oxidetall oil fatty acid reaction products; isooctyl phenol-ethylone oxide reaction products; propylene oxide-ethylene oxide reaction products; and combinations of isooctyl phenol-ethylene oxide with coconut oil fatty acid-ethylene oxide reaction products.

The halogenated bisphenols and the polyhalo-salicylanilides can be added to the soap or detergent by any suitable method which results in a uniform distribution of the germicides throughout the entire mass. A highly satisfactory dispersion method of carrying out the addition step is described more fully in copending application Ser. No. 263,302, filed Dec. 26, 1951, now abancloned.

Specific examples illustrating the invention are set out as follows:

EXAMPLE I The procedure employed for determining the minimum effective dose (M.E.D.) represents a variation of a method published in the Journal of General Micro biology, vol. 10, No. 2, April 1954, on Observations on the Mode of Action of Antibiotic synergism and Antagonism, Department of Microbiology, University of California School of Medicine. In place of the plate counts used in the published method, the end points of chemical activity in the present method was taken as that point at which no growth was apparent in the broth tubes.

The minimum effective dose of 2,2 dihydroxy- 3,5,6,3',5',6 hexaclorodiphenyl methane and S-chlorosalicylic acid-3,4'-dichloroanilide was first determined by diluting the prepared stock solutions of the two test chemicals in a series of tubes containing 10 ml. of nutrient broth culture medium. Each successive tube in the series contained the test chemicals at one-half the concentration of the previous tube. 0.1 ml. of a 1-10 dilution of a 24-hour broth culture of the test Organism M. pyogenes var. aureus was then added to each of the broth tubes in the series. The period of incubation for all types was 48 hours at a temperature of 37 C. The end point of minimum effective dose of chemical was taken as that point at which no growth was apparent in the highest dilution of the chemical in the broth tube.

After determining the minimum effective dose of both the test chemicals, the two agents were next combined in a series of broth tubes at a concentration in broth at subinhi'bitory and near subinhibitory level of both chemicals. Each tube in the series of 16 tubes contained the test chemicals in a different ratio. Inoculation with the test organisms M. pyogenes var. aureus was made in each tube in the series by adding to each tube 0.1 ml. of a 1-10 dilution of a 24-hour broth culture of the organism. The incubation period was 48 hours at a temperature of 37 C. The determination of synergistic activity was made in the tube or tubes having the lowest subinhibitory concentration of both the test chemicals showing no apparent growth of the test organism. 'The results of these tests is set forth in Table 1 wherein the minimum effective dose in micrograms per ml. is given.

Antiseptic detergent compositions exemplary of the present invention were prepared by intimately mixing the ingredients listed in Tables 14 below to form composites containing 0.5%, 1.0%, 2.0% and 3% by weight active ingredient.

TABLE 1.-0.5% BY WEIGHT ACTIVE INGREDIENT" A B C D Composition E 1. Neutral white toilet soap containing about 20% by weight of sodium coco soap and 80% by weight of sodium tallow soap 99. 50 99. 50 99. 50 99. 5O 99. 50 2. 2,2-dihydroxy-3,5,6,3,5',6-

hexaehlorodiphenyl methane 3. 2,2-dihydroxy-3,5.3'.5-tetrachlorodiphenyl sulfide 4. 5-chlorosalicylic acidi TABLE 2.l.0% BY WEIGHT ACTIVE INGREDIENT A B C D TABLE 3.2% BY WEIGHT ACTIVE, INGREDIENT A. B C D Composition 1. Neutral white toilet soap containing about 20% by weight of sodium coco soap and 80% by weight of sodium tallow soap 2v 2,2-dihydroxy3,5,6,3,5,6-

hexachlorodiphenyl methane 3. 2,2-dihydroxy'3,5,3,5-totra chlorodiphenyl sulfide 4. 5-chlorosalicylic acid-3,4-

dichloroanilide TABLE 4.3% BY WEIGHT ACTIVE INGREDIENT A B C D dichloranilide Aliquots of each of the above described compositions containing 0.5%, 1.0%, 2.0% and 3.0% respectively 'by weight active ingredient were added to nutrient agar medium so as to give in each instance a concentration of 0.125 part per million of active ingredient in agar.

[Amount of growth (M.

6 The agar in each case was then poured into a petri dish, allowed to harden and then streaked with a 24 hour broth culture of M. pyogenes var. aureus diluted 1-10. The incubation in each case was 48 hours at a temperature of 37 C. The degree of growth is noted in Tables 5 8 as follows:

TABLE 5.-0.5% BY WEIGHT OF ACTIVE INGREDIENTS Composition A B C D E 1. Period of incubation 48 48 48 48 48 2. Amount of growth 1+ 1+ 3+ 0 0 Norm-See legend at end of Table 8.

TABLE 6.1.0% BY WEIGHT OF "ACTIVE INGREDIENTS Composition A B C D E 1. Period of incubation 48 48 48 48 48 2. Amount of growth 2+ 2+ 3+ 0 0 N o'rE.See legend at end of Table 8.

TABLE 7.-2% BY WEIGHT OF ACTIVE INGREDIENTS Composition A B C D E 1. Period of incubation 48 48 48 48 48 2. Amount of growth 3+ 3+ 3+ 1+ 1+ No'rE.See legend at end of Table 8.

TABLE 8.3% BY WEIGHT 0F ACTIVE INGREDIENTS Composition A B C D E 1. Period of incubation a. 48 48 48 48 48 2. Amount of growth 2+ 2+ 3+ 1+ 1+ LEGEND.O=NO growth. 1+=Very slight growth. 2+=Light to moderate growth. 3+=Normal heavy growth.

Both individual germicides and combinations of germicides were incorporated in a soap containing 20% sodium coco soap and sodium tallow soap, a noionic detergent, and an anionic synthetic detergent at a total concentration of 1% basis soap and 1% detergent solution prepared. Aqueous solutions of the individual germicides were also prepared at a concentration of p.p.-m. and further diluted to 10 ppm. The 1% detergent solutions were also diluted with distilled water to 10 p.p.m. total germicide. Aliquot amounts of these solutions were then added to liquid nutrient agar so as to give the concentrations of the germicide in agar in Table 1 below. Plates were poured, allowed to harden and streaked with a 24- hour broth culture of M. pyogenes var. aureus F.D.A. strain 20 9. The plates were incubated 48 hours at 37 C. and the amount of growth in the plates noted. The results are given in Table 1 as follows:

TAB LE 1 pyogenes) on agar plates with agar containing aliquots of 5-chlorosalicyllc acid-3',4- dichloroanilide and a halogenated bisphenol incorporated in the following agents] Nonionic Anionic Synthetic Water Soap Detergent Detergent P.p.m. Total Germicide Basis Agar Anoblal 0 0 0 3+ 0 0 1+ Actamer 3+ 3+ 3+ 3+ 1+ 3+ 3+ Anob.plusAct 0 0 0 1+ 0 0 0 2 G-ll -.0 0' 2+ 3+ 0 2+ 3+ Anob.pluS G-ll 0 0 0 1+ 0 0 0 G-5 3+ 3+ 3+ 3+ 3+ 3+ Anob. plus G-5 -0 0 0 1+ 0 0 0 G-ll- 1+ 3+ 3+ 3+ 3+ 3+ 3+ Anob. plus G-11-S 0 0 0 2+ 0 0 0 TABLE 1-Continued [Amount of growth (M. pyogenes) on agar plates with agar containing aliquots of 5-chlorosa1icylic acid-4-chloroanilide and a halogenated bisphenol incorporated in the following agents] Nonionic Anionic Synthetic Water Soap Detergent Detergent P.p.m. Total Germicide Basis Agar AnobialAn 1+ 2+ 3+ 3+ 1+ 3+ 3+ 0 0 3+ 3+ 0 0 2+ 3+ 0 0 1+ 3+ 1+ 3+ 3+ 3+ 0 1+ 2+ 3+ S A-A&G11S 0 0 1+ 3+ 3+ CODE.--0=NO growth on plates.

Materials Used:

Anobial-2-hydroxy-S-ehlorobenzoic acid 34-dichloroauilide. Actamer2,2-thiobis (4,6dichlorophenol). G112,2-dihydroxy hexachloro diphenyl methane. G52,2-dihydroxy-3,5,6,3, 5 ,6-tetrach1orodiphenyl methane. G11S2,2-dihydroxy hexachlorodiphenyl sulfide.

Anobial A11. or A-A-Z-hydroxy-5tehlorobenzoic acid-4-chloroanilide.

EXAMPLE IV Experiments were carried out to determine the variation of synergistic effect with change in the ratio of compound active ingredient. All experiments were carried out in a toilet soap medium. For this purpose the individual germicidal compounds or mixtures of compounds were incorporated at total germicidal levels of 0.5%, 1.0%, 2.0% and 3.0%, respectively, into a conventional toilet soap base containing coconut oil and 80% inedible tallow. The soaps were dissolved in water to give 0.5%, 1.0%, 2.0% and 3.0% soap solutions respectively, which correspond to a 0.005% 0.01% 0.02% and 0.0 3 concentration of germicide. The bacteriological evaluations were carried out with a modified streak method. Aliquots of the 0.5%, 1.0%, 2.0% and 3.0% test soap solutions were added to measured amounts of liquid glucose tryptone extract agar, and the resulting mixture was poured into petri dishes. As soon as the agar had hardened, its surface was streaked with a 24-hour broth culture of S. aureus F.D.A. strain No. 209. The plates were incubated for 48 hours at 37 C. and the amount of growth was recorded.

In this manner a ratio study of the synergistic pair 2,2-dihydroxy-3,5,6,3',5,6 hexachlorodiphenyl methane and S-chlorosalicyclic acid-3',-4-dichloroanilide (anobial) was carried out, the results of which are summarized in Table 1. Analogous study of the pair 2,2-dihydroxy-3,5, 3',5-tetrachlorodiphenyl sulfide (bithionol) and 5-chlorosalicyclic acid-3,4'-dichloroanilide (anobial) was carried out by using the same method, and the results of this study are summarized in Table 2.

TABLE 1 Antibacterial effectiveness of varied ratios of hexachlorophene and S-chlorosalicylic acid 3',4dichlor0anilide (anobial) in soap (modified agar streak method).

Bacterial Growth Ratings CODE.0=N0 growth. 1=Slight growth.

2=Moderate growth. 3= Heavy growth.

TABLE 2 Antibacterial eflectiveness of varied ratios of 2,2'-dihydroxy-3,5,3,5'-tetrachlorodiphenyl sulfide (bithionol) and anobial in soap (modified agar streak methods).

1+=Light growth. 2+=Modorate growth. 3+=Normal heavy growth.

Bacterial Growth Ratings Total Antibacterial Agent C0nE.-0=No growth. 1=Slight growth. 2=Moderate growth. 3= Heavy growth.

As indicated above, synergistic results were obtained when the ratio of the halogenated bisphenols (hexachlorophone or bithionol) to anobial was between 10-90% by weight of the halogenated bisphenols to -10% by weight of the anobial.

We claim:

1. An antiseptic detergent composition consisting essentially of soap and about 1% by weight based upon the soap of a mixture of equal parts by weight of 2,2'-dihydroxy-3,5,6,3',5,6-hexachlorodiphenyl methane and 5- chlorosalicylic acid-3,4-dichloroanilide.

2. An antiseptic detergent composition consisting essentially of soap and about 1% by weight based upon the soap of a mixture of equal parts by weight of 2,2'-dihydroxy-3,5,6,3',5,6'-hexachlorodiphenyl methane and 5- chlorosalicylic acid-4-chloroanilide.

3. An antiseptic detergent composition consisting essentially of soap and about 1% by weight based upon the soap of a mixture of equal parts by weight of 2,2-dihydroxy-3,5,3,5'-tetrachlorodiphenyl methane and 5 -chlorosalicylic acid-4-chloroanilide.

4. An antiseptic detergent composition consisting essentially of a synthetic detergent and about 1% by weight based upon the detergent of a mixture of equal parts by weight of 2,2'-dihydroxy-3,5,6,3',5,6'-hexachlorodiphenyl methane and S-chlorosalicylic acid-3,4-dichloroanilide.

5. An antiseptic detergent composition consisting essentially of a synthetic detergent and about 1% by weight based upon the detergent of a mixture of equal parts by weight of 2,2'-dihydroxy-3,5,6,3',5,6-hexachlorodiphenyl methane and S-chlorosalicylie acid-4-chloroanilide.

6. An antiseptic detergent composition consisting essen tially of a synthetic detergent and about 1% by weight based upon the detergent of a mixture of equal parts by weight of 2,2 dihydroxy 3,5,3',5' tetrachlorodiphenyl methane and 5-chlor0salicylic acid-4-chloroanilide.

7. An antiseptic detergent composition consisting essentially of soap and about 2% by weight based upon the soap of a mixture of equal parts by weight of 2,2'-dihy- 9 droxy-3,5,6,3',5',6'-hexachlorodipheny1 methane and 5- chlorosalicylic acid-3',4'-dichloroanilide.

8. An antiseptic detergent composition consisting essentially of soap and from about 0.5% to about 3% by weight based upon the soap of a synergistic combination of 2,2'-dihydroxy-3,5,6,3,5,6-hexachlorophenyl methane and 5-chlorosalicylic acid-3',4'-dichloroanilide, the ratio of said hexachlorophenyl methane to said dichloroanilide being from 20 to 90% by weight of the hexachlorophenyl methane to about 80 to 10% by Weight of said dichloroanilide at a total combined concentration of at least 0.04 part per million.

9. An antiseptic detergent composition consisting essentially of soap and from about 0.5% to about 3% by weight based upon the soap of a mixture of 2,2'-dihydrxy-3,5,6,3',5',6'-hexachlorophenyl methane and -chlorosalicylic acid-3,4-dichloroanilide in a ratio of 40 to 90% by weight of said hexachlorophenyl methane to about 60 to by weight of said dichloroanilide at a total combined concentration of at least 0.02 part per million.

10. An antiseptic detergent composition consisting essentially of soap and about 1% by Weight of a synergistic combination of a halogenated bisphenol selected from the group consisting of 2,2'-dihydroxy-3,5,6,3',5',6'-hexachlorophenyl methane, 2,2'-dihydroXy-3,5,3,5'-tetrachlorodiphenyl methane and 2,2'-dihydroxy-3,5,6,3,S',6-hexach1orodiphenyl sulfide and a polyhalo-salicylanilide selected from the group consisting of S-chlorosalicylic acid-3',4'- dichloroanilide and S-chlorosalicylic acid-4-ch1oroanilide References Cited UNITED STATES PATENTS 2,353,735 7/1944 Kunz 167-31 2,544,826 3/1951 Craige 167-31 2,606,210 8/1952 Moyle 16731 2,764,614 9/1956 Meyer 16731 2,818,390 12/1957 Beaver 167-31 X 2,865,861 12/1958 Stephens 167-31 3,057,920 10/ 1962 Schramm 167-31 FOREIGN PATENTS 745,607 2/ 1956 Great Britain. 1,130,335 2/1957 France.

OTHER REFERENCES Berk: Industrial and Eng. Chem., volume 40, pages 262-267, January-June 1948.

Lewis: Perf. and Ess. Oil Rev., pages 298-302, Sep tember 1954.

Hopley et al., Sindor Corp. Tech. Bull. D-2 G4 (Dichlorophene), page 10, July 1956.

ALBERT T. MEYERS, Primary Examiner.

J. GOLDBERG, Assistant Examiner.

US. Cl. X.R. 

10. AN ANTISEPTIC DETERGENT COMPOSITION CONSISTING ESSENTIALLY OF SOAP AND ABOUT 1% BY WEIGHT OF A SYNERGISTIC COMBINATION OF A HALOGENATED BISPHENOL SELECTED FROM THE GROUP CONSISTING OF 2,2''-DIHYDROXY-3,5,6,3'',5'',6''-HEXACHLOROPHENYL METHANE, 2,2''-DIHYDROXY-3,5,3'',5''-TETRACHLORODIPHENYL METHANE AND 2,2''-DIHYDROXY 3,5,6,3'',5'',6''-HEXACHLORODIPHENYL SULFIDE AND A POLYHALO-SALICYLANILIDE SELECTED FROM THE GROUP CONSISTING OF 5-CHLOROSALICYLIC ACID-3'',4''DICHLOROANILIDE AND 5-CHLOROSALICYLIC ACID-4-CHLOROANILIDE AND WHEREIN THE RATIO BY WEIGHT OF SAID BISPHENOL TO SAID POLYHALO-SALICYLANILIDE IS 1 TO
 1. 